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Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging.Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed.A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts.CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach.

Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV. Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model. Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea. Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.

Exploiting human mesenchymal stem cells (hMSCs) was proposed as a promising therapeutic approach for cardiovascular disease due to their capacity to differentiate into cardiac cells. Though modulation of the intracellular signaling pathways dominantly WNT/β catenin and transforming growth factor-β (TGF-β) have been reported to promote differentiation of hMSCs into cardiomyocytes in the prevailing literature, a safe and reproducible system for their clinical application has not yet turned into reality. In the present study, the molecular docking-based strategy was first applied for evaluating the potency of some natural phenolic compounds in the modulation of Wnt and TGF-β signaling pathways using a vital class of crystallographic protein structures of WNT signaling regulators such as Frizzled, Disheveled, GSK3-β, β-catenin, LRP 5/6 extracellular domain, Tankyrase and their variety of active pockets. Then, the impacts of plant-derived chemical compounds on the regulation of the relevant signals for the differentiation of hMSCs into the definitive mesoderm lineage and cardiac progenitors were assessed in vitro. Data obtained revealed the synergistic activity of Wnt and TGF-β superfamily to direct cardiac differentiation in human cardiogenesis by comparing cardiac gene expression in the presence and absence of the TGF-β inhibitors. We found that the inhibitory effect of canonical Wnt/β-catenin is sufficient to cause proper cardiomyocyte differentiation, but the TGF-β pathway plays a vital role in enhancing the expression of the cardiomyocyte-specific marker (cTnT). It was found that quercetin, a p38MAPK inhibitor with the high energy dock to the active pocket of Wnt receptors, promotes cardiac differentiation via the inhibition of both Wnt and non-Smad TGF-β pathways. Altogether, data presented here can contribute to the development of a feasible and efficient cardiac differentiation protocol as an "off-the-shelf" therapeutic source using novel natural agents for cardiac repair or regeneration.

Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the

The generation of complex physicochemical signals on the surface of biomedical materials is still challenging despite the fact that a broad range of surface modification methods have been developed over the last few decades. Colloidal self-assembled patterns (cSAPs) are combinations of unique colloids differing in size and surface chemistry acting as building blocks that can be programmed to generate surface patterns with exquisite control of complexity. This study reports on producing a variety of pre-modified colloids for the fabrication of cSAPs as well as post-assembly modifications to yield complex surfaces. The surface of cSAPs presents hierarchical micro- and nanostructures, localized hydrophilic/hydrophobic characteristics, and tunable surface functionality imparted by the individual colloids. The selected cSAPs can control bacterial adhesion (S. aureus, P. aeruginosa, and E. coli) and affect the cell cycle of human bone marrow stem cells (hBMSCs). Moreover, in a mouse subcutaneous model, cSAPs with selective [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium (SBMA) modification can reduce the inflammatory response after being challenged with bacteria. This study reveals that functionalized cSAPs are versatile tools for controlling cellular responses at biointerfaces, which is instructive for biomaterials or biodevices.

Twenty-one gliomas in patients aged 0-21 years were evaluated for drug sensitivity by ex vivo expanded circulating tumor cells (CTC). The results were correlated with clinical outcomes. Venous blood samples were obtained prior to drug treatment. Peripheral blood mononuclear cells were processed in a 3D cell culture system (EVA Select™, Cancer Free Biotech Ltd., Taipei, Taiwan) and cultured for 3 weeks. Expanded CTCs were successfully cultured into organoids from 18 out of 21 patients and were analyzed for ATP abundance. Staining with CD45, a marker for blood cells, and pancytokeratin, a marker for keratinocytes, was performed on the cultured cells. Staining of GFAP, a marker of glioma cells, was performed in a subset of samples. These cells were then tested in cytotoxicity assays in triplicate with a panel of chemotherapeutic and targeted agents at clinically relevant concentrations. The surviving fraction was normalized to a buffer-only control. Based on the percentage of cell viability, the agent was chosen for clinical treatment. Comparing the results among low-grade glioma (LGG; n = 6), diffuse midline glioma (DMG; n = 4), and high-grade glioma (HGG, n = 8; including glioblastoma multiforme [GBM; n = 5]), the mean surviving fraction to temozolomide was similarly high across the three tumor types (LGG vs. DMG vs. HGG = 57.5% vs. 50.6% vs. 49.5%, respectively). 6 of 6 patients in the LGG group showed CTC sensitivity to at least one chemotherapeutic agent tested. The clinical response of patients treated with selected agents was evaluated with the RANO criteria at 6 months after initiation of treatment. Among the 24 agents tested with clinical correlation, the CTC surviving fraction after exposure to the agent was significantly higher in patients who had progressive disease within 6 months (n = 11; 68%) vs. in patients with no progression at 6 months (n = 13; 39%; P = 0.039). Treating CTCs with histone deacetylase inhibitors in vitro resulted in a consistently lower surviving fraction (15.1% ± 12.0%) for DMG and HGG/GBM; however, clinical correlation was not available. The 1 patient with clinical correlation with HGG had a 34.9% surviving fraction to a Tyrosine kinase inhibitor (TKI) in vitro and showed a 42.9% shrinkage at 6 months after treatment with the TKI. The expansion of CTCs in patients with relapsed/refractory pediatric gliomas provides the ability to test drug sensitivity of patient-derived organoids. Our data suggest a correlation between the ex vivo drug sensitivity of CTCs and clinical response. Citation Format: Yen-Lin Liu, Yin-Ju Chen, Shu-Huey Chen, Yu-Mei Liao, Wu Shih-Pei, Yi-Hsuan Chen, Wan-Ling Ho, Liang-Yi Juo, Chia-Yau Chang, Jinn-Li Wang, Min-Yu Su, Pei-Chin Lin, Shih-Chung Wang, James S. Miser, Tai-Tong Wong, Yuan-Hung Wu, Peng Yuan Wang, Thierry Burnouf, Jeng-Fong Chiou, Long-Sheng Lu. Application of in vitro drug screening of circulating tumor cells in pediatric glioma therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6723.

Objective The aim of this study was to investigate the expression of TP53-inducible glycolysis and apoptosis regulator (TIGAR) and its relationship with clinical pathology and prognosis; and to analyze the correlation between TIGAR expression and 18F-labeled fluoro-2-deoxyglucose (18F-FDG) PET/computed tomography (CT) parameters in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We retrospectively analyzed the data of 23 patients who underwent preoperative 18F-FDG PET/CT examinations and were confirmed to have PDAC by postoperative pathology. TIGAR was detected using immunohistochemistry. The relationships between TIGAR expression and clinicopathology and its value in predicting the prognosis of patients with PDAC were analyzed. The correlations between TIGAR expression and 18F-FDG PET/CT parameters [standard uptake value (SUV) max, SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were analyzed. Results The expression of TIGAR was low in 34.8% of patients and high in 65.2% of patients. There was no correlation between TIGAR expression and clinicopathology. The overall survival of patients with high TIGAR expression was significantly shorter than that of patients with low TIGAR expression (11.2 vs. 35.4 months). The 18F-FDG PET/CT parameters: SUVmax, SUVmean, SUVpeak, MTV, and TLG were positively correlated with TIGAR expression, but only the MTV correlation with TIGAR expression was statistically significant. Conclusion TIGAR is highly expressed in PDAC. Its expression is independent of clinicopathological data and can be used as an independent prognostic factor. TIGAR expression was significantly positively correlated with the 18F-FDG PET/CT parameter MTV.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system provides a groundbreaking genetic technology that allows scientists to modify genes by targeting specific genomic sites. Due to the relative simplicity and versatility of the CRISPR/Cas system, it has been extensively applied in human genetic research as well as in agricultural applications, such as improving crops. Since the gene editing activity of the CRISPR/Cas system largely depends on the efficiency of introducing the system into cells or tissues, an efficient and specific delivery system is critical for applying CRISPR/Cas technology. However, there are still some hurdles remaining for the translatability of CRISPR/Cas system. In this review, we summarized the approaches used for the delivery of the CRISPR/Cas system in mammals, plants, and aquacultures. We further discussed the aspects of delivery that can be improved to elevate the potential for CRISPR/Cas translatability.

The recent rise of antibiotic resistance amongst Staphylococcus aureus (S. aureus) populations has made treating Staph-based infections a global medical challenge. Therapies that specifically target the peptidoglycan layer of S. aureus have emerged as new treatment avenues, towards which bacteria are less likely to develop resistance. While the majority of antibacterial polymers/oligomers have the ability to disrupt bacterial membranes, the design parameters for the enhanced disruption of peptidoglycan outer layer of Gram-positive bacteria remain unclear. Here, the design of oligomeric structures with favorable conformational characteristics for improved disruption of the peptidoglycan outer layer of Gram-positive bacteria is reported. Molecular dynamics simulations were employed to inform the structure design and composition of cationic oligomers displaying collapsed and expanded conformations. The most promising diblock and triblock cationic oligomers were synthesized by photo-induced atom transfer radical polymerization (photo ATRP). Following synthesis, the diblock and triblock oligomers displayed average antibacterial activity of ~99% and ~98% for S. aureus and methicillin-resistant S. aureus (MRSA), respectively, at the highest concentrations tested. Importantly, triblock oligomers with extended conformations showed significantly higher disruption of the peptidoglycan outer layer of S. aureus compared to diblock oligomers with more collapsed conformation, as evidenced by a number of characterization techniques including scanning electron, confocal and atomic force microscopy. This work provides new insight into the structure/property relationship of antibacterial materials and advances the design of functional materials for combating the rise of drug-resistant bacteria.

Retinal neovascularization is a severe complication of proliferative diabetic retinopathy (PDR). MicroRNAs (miRNAs) are master regulators of gene expression that play an important role in retinal neovascularization. In this study, we show that miR-143-3p is significantly downregulated in the retina of a rat model of oxygen-induced retinopathy (OIR) by miRNA-sequencing. Intravitreal injection of synthetic miR-143 mimics significantly ameliorate retinal neovascularization in OIR rats. miR-143 is identified to be highly expressed in the neural retina particularly in the ganglion cell layer and retinal vasculature. In miR-143 treated cells, the functional evaluation showed a decrease in cell migration and delayed endothelial vessel-like tube remodeling. The multiomics analysis suggests that miR-143 negatively impacts endothelial cell activity through regulating cell-matrix adhesion and mediating hypoxia-inducible factor-1 signaling. We predict hub genes regulated by miR-143 that may be involved in mediating endothelial cell function by cytoHubba. We also demonstrate that the retinal neovascular membranes in patients with PDR principally consist of endothelial cells by CIBERSORTx. We then identify 2 hub genes, thrombospondin 1 and plasminogen activator inhibitor, direct targets of miR-143, that significantly altered in the PDR patients. These findings suggest that miR-143 appears to be essential for limiting endothelial cell-matrix adhesion, thus suppressing retinal neovascularization.

Surface topography-induced lineage commitment of human bone marrow stem cells (hBMSCs) has been reported. However, this effect on hBMSC differentiation toward retinal pigment epithelium (RPE)-like cells has not been explored. Herein, a family of cell culture substrates called binary colloidal crystals (BCCs) was used to stimulate hBMSCs into RPE-like cells without induction factors. Two BCCs, named SiPS (silica (Si)/polystyrene (PS)) and SiPSC (Si/carboxylated PS), having similar surface topographies but different surface chemistry was used for cell culture. The result showed that cell proliferation was no difference between the two BCCs and tissue culture polystyrene (TCPS) control. However, the cell attachment, spreading area, and aspect ratio between surfaces were significantly changed. For example, cells displayed more elongated on SiPS (aspect ratio ~7.0) than those on SiPSC and TCPS (~2.0). The size of focal adhesions on SiPSC (~1.6 µm

Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other proinflammatory cytokines. TAK1 is also a key mediator of proinflammatory signals and plays an important role in maintaining vascular integrity upon proinflammatory cytokine stimulation such as TNFα. However, its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. Here, we investigate the regulatory role of TAK1 in human endothelial cells responding to inflammatory stimuli and in a rat model of oxygen-induced retinopathy (OIR) featured retinal neovascularization. Using TAK1 knockout human endothelial cells that subjected to inflammatory stimuli, transcriptome analysis revealed that TAK1 is required for activation of NFκB signaling and mediates its downstream gene expression related to endothelial activation and angiogenesis. Moreover, pharmacological inhibition of TAK1 by 5Z-7-oxozeaenol attenuated angiogenic activities of endothelial cells. Transcriptome analysis also revealed enrichment of TAK1-mediated NFκB signaling pathway in the retina of OIR rats and retinal neovascular membrane from patients with proliferative diabetic retinopathy. Intravitreal injection of 5Z-7-oxozeaenol significantly reduced hypoxia-induced inflammation and microglial activation, thus attenuating aberrant retinal angiogenesis in OIR rats. Our data suggest that inhibition of TAK1 may have therapeutic potential for the treatment of retinal neovascular pathologies.

It is generally accepted that the distal resection margin of intermediate- to low-lying rectal cancer should be greater than 2 cm and at least 1 cm in special cases. This study intends to investigate whether a distal resection margin ≤ 1 cm affects tumor outcomes for patients with intermediate- to low-lying rectal cancer.A systematic review of the literature was conducted. Sixteen studies included data for distal resection margins ≤ 1 cm (1684 cases) and 1 cm (5877 cases), and 5 studies included survival data. Meta-analysis was used to compare the local recurrence rate and long-term survival of patients with distal resection margins or ≤ 1 cm.The local recurrence rate in the ≤ 1-cm margin group (9.5%) was 2.3% higher than that in the 1-cm margin group (7.2%) according to a fixed-effects model (RR [95% CI] 1.42 [1.18, 1.70], P 0.001). The overall survival results of the five 1-cm margin studies showed an HR (95% CI) of 0.96 (0.75, 1.24) (P = 0.78). Subgroup analysis showed that the local recurrence rate in the subgroup with perioperative treatment was 1.2% lower in the ≤ 1-cm margin group (8.3%) than in the 1-cm margin group (9.5%) (RR [95% CI] 0.97 [0.63, 1.49], P = 0.90). In the surgery alone subgroup, the local recurrence rate was 4.7% higher in the ≤ 1-cm margin group (12.4%) than in the 1-cm group (7.7%) (RR [95% CI] 1.76 [1.09, 2.83], P = 0.02).For patients with intermediate- to low-lying rectal cancer undergoing surgery alone, a distal resection margin ≤ 1 cm may be not safe.

Patients with stage IIA rectal cancer have a higher survival rate but side effects from chemoradiotherapy; thus, whether neoadjuvant therapy should be performed for stage IIA rectal cancer is controversial. This study aimed to compare the survival outcomes of patients with stage IIA rectal cancer with or without neoadjuvant chemoradiotherapy.Patients with stage IIA rectal cancer between 2010 and 2015 were included through the Surveillance, Epidemiology, and End Results database. Propensity score matching was used to reduce the impact of confounding factors. Survival curves were plotted using the Kaplan-Meier method, and survival differences were assessed using the log-rank test.There were no significant differences in overall survival and cancer-specific survival between the neoadjuvant chemoradiotherapy and surgery groups (P=0.973 and 0.983). Compared with the surgery group, the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had a better overall survival (P=0.007). Subgroup analysis showed that the neoadjuvant chemoradiotherapy + surgery + chemotherapy group had better overall survival compared to the surgery group in the subgroup containing preoperative high-risk factors (P=0.003) but not in the low-risk subgroup (P=0.685).There is no evidence that neoadjuvant chemoradiotherapy + surgery can improve overall survival and cancer-specific survival compared to surgery alone in patients with stage IIA rectal cancer. Neoadjuvant chemoradiotherapy + surgery + chemotherapy can improve overall survival compared to surgery alone, but only in patients with preoperative high-risk factors. We suggest that patients with no preoperative high-risk factors may be considered for surgery alone, neoadjuvant chemoradiotherapy + surgery + chemotherapy is recommended for patients with preoperative risk factors.

Conventional methods of neuronal differentiation in human induced pluripotent stem cells (iPSCs) are tedious and complicated, involving multistage protocols with complex cocktails of growth factors and small molecules. Artificial extracellular matrices with a defined surface topography and chemistry represent a promising venue to improve neuronal differentiation

Aberrant growth of blood vessels (neovascularization) is a key feature of severe eye diseases that can cause legal blindness, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). The development of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of ocular neovascularization. Novel proangiogenic targets, such as angiopoietin and platelet-derived growth factor (PDGF), are under development for patients who respond poorly to anti-VEGF therapy and to reduce adverse effects from long-term VEGF inhibition. A rapidly advancing area is gene therapy, which may provide significant therapeutic benefits. Viral vector-mediated transgene delivery provides the potential for continuous production of antiangiogenic proteins, which would avoid the need for repeated anti-VEGF injections. Gene silencing with RNA interference to target ocular angiogenesis has been investigated in clinical trials. Proof-of-concept gene therapy studies using gene-editing tools such as CRISPR-Cas have already been shown to be effective in suppressing neovascularization in animal models, highlighting the therapeutic potential of the system for treatment of aberrant ocular angiogenesis. This review provides updates on the development of anti-VEGF agents and novel antiangiogenic targets. We also summarize current gene therapy strategies already in clinical trials and those with the latest approaches utilizing CRISPR-Cas gene editing against aberrant ocular neovascularization.

A scaffold was fabricated to synergistically encapsulate living human adipose-derived stem cells (hASCs) and platelet-rich plasma (PRP) based on a vapor-phase sublimation and deposition process. During the process, ice templates were prepared using sterile water as the solvent and were used to accommodate the sensitive living cells and PRP molecules. Under controlled processing conditions, the ice templates underwent vapor sublimation to evaporate water molecules, while at the same time, vapor-phase deposition of poly

The fusion of skeletal myoblasts is a critical step in myotube formation and muscle maturation. Previously, we demonstrated that nanogrooves improved myoblast fusion via end-to-end fusion, which in turn generated parallel myotubes. However, the effect of serum components on the end-to-end fusion mechanism is unclear. In the current study, the synergistic effect of nanogrooves and human platelet lysate (hPL) on the growth and fusion of skeletal myoblasts was studied. Four types of nanogrooves (400 and 800 nm width; 100 and 400 nm depth) were used. Cell spreading, growth, and differentiation were screened on these nanogrooves in media formulated with hPL or fetal bovine serum (FBS), along with the flat substrate as a control group. The results showed that the deeper nanogrooves induced better alignment of myoblasts. hPL-adapted skeletal myoblasts (i.e., myoblasts@hPL) showed a smaller cell size with a more elongated morphology than myoblasts@FBS. During cell growth, the expression of myogenic genes (Myf5, MyoD, and MyoG) in myoblasts@hPL was lower than in myoblasts@FBS. During cell differentiation, myoblasts@hPL also expressed a lower level of myogenic and myosin heavy chain (MHC) genes. MHC-positive myoblasts@hPL without myotubes were found on all surfaces. Myomaker, an essential myoblast fusion gene, was upregulated during growth but downregulated during differentiation in myoblasts@hPL. Fibronectin-coated surfaces facilitate cell spreading and growth but still cannot support myoblast@hPL fusion. The results implied that hPL either lacks promotor factors or contains inhibitors on mouse skeletal myoblast fusion. This study reveals the effect of biophysical and biochemical cues on myoblast fusion and their potential for muscle tissue engineering.

The surface properties of biomaterials are crucial at controlling biological interactions. Cells or tissues sense different stimuli from surfaces and respond accordingly. A number of studies have reported that fabricating complex stimuli-presenting surfaces is beneficial for mimicking and understanding the in vivo scenario where multi-physicochemical cues are present. Biological responses toward these surfaces could be either negative, such as immune responses, or positive, such as tissue regeneration. An ideal material surface should, therefore, be multifunctional, triggering the desired biological process and suppressing the unwanted side effects. The methods for material surface decoration can be very sophisticated, depending on the applications such as biosensors, medical devices, and/or implants. To date, decorating material surfaces with complex chemistries and topographies is still challenging, and methods are not straightforward. The majority of the methods require multiple steps and combinational approaches that include mask-based techniques, lithography, wet or dry etching, wet chemistry, or vapor-based coatings, among others. Although these methods have been established in the laboratory, easy-to-access and straightforward approaches need to be explored. This Review summarizes the state-of-the-art techniques for generating patterned multichemical and multitopographic signals on material surfaces, and the potential of having these surfaces in biointerface applications.

Ralstonia solanacearum is a common plant bacterium, and the improper use of chemicals to control this bacterium is harmful to the environment. Many undeveloped aromatic plants and green plant waste can be used for the preparation of essential oils (EOs). EOs have various biological activities, such as bacteriostatic, insecticidal and anti-oxidation, and are currently in the exploration stage for the control of R. solanacearum. In the present study, the inhibitory activity of ten EOs against R. solanacearum was determined by an antibacterial test. To prolong the duration of antibacterial activity, microcapsules of EOs were prepared by the complex coacervation method, and the optimal preparation conditions were obtained by central composite design method. The results showed that cinnamon EOs had the strongest antibacterial activity. For GIM1.71, GIM1.74, GIM1.76, GMI1000 and RS-5, the EC50 values of cinnamon EOs were 0.055 mg/mL, 0.071 mg/mL, 0.03 mg/mL, 0.067 mg/mL and 0.063 mg/mL, respectively. The preparation condition of cinnamon EOs microcapsules was as follows: the core-wall ratio was 4.35:1, the ratio of chitosan and sodium alginate was 0.15:1, and the calcium chloride concentration was 0.95 wt%. The encapsulation efficiency was 87.32%, and the average particle size of microcapsule was 870.4 μm. The release rate of microcapsule was 44.53% at 100 °C for 6 h and the release of the core materials in microcapsules was in line with Korsmeyer–Peppas release kinetics. Microcapsules placed at room temperature for 7 days still had significant antibacterial activity against five species of R. solanacearum. Due to its good stability and antibacterial activity, cinnamon EOs microcapsules will have great market application prospects as antibacterial agents.

Extracellular matrix (ECM) of the tumor microenvironment (TME), including topography and biological molecules, is crucial in cancer cell attachment, growth, and even the sensitivity to the chemo and cell drugs treatment. This study hypothesizes that mimic ECM structures can alter the attachment and drug sensitivity of cancer cells. A family of artificial ECM called colloidal self-assembled patterns (cSAPs) was fabricated to mimic tumor ECM structures. Cell adhesion, proliferation, and drug sensitivity of the A549 non-small cell lung cancer (NSCLC) cells were studied on 24 cSAPs, named cSAP#1-cSAP#24, where surface topography and wettability were distinct. The results showed that cell adhesion and cell spreading were generally reduced on cSAPs compared to the flat controls. In addition, the synergistic effect of cSAPs and several chemo drugs on cell survival was investigated. Interestingly, A549 cells were more sensitive to the combination of doxorubicin and cSAP#4. Under this condition, the focal adhesion kinase (FAK) signaling was downregulated while p53 signaling was upregulated, confirmed by real-time PCR and western blot analysis. It indicates that the specific surface structure could induce higher drug sensitivity and in vitro anoikis of A549 cells. A serum alternative, human platelet lysate (hPL), and different cSAPs were examined to verify our hypothesis. The result further confirmed that cell adhesion strongly affected the drug sensitivity of A549 cells. This study demonstrates that the tumor ECM is vital in cancer cell activity and drug sensitivity; therefore, it should be considered in drug discovery and therapeutic regimens.